A Propranolol-Ulceration Dispute Plays Out in JAAD's Unindexed Pages

A reply letter posted this week to the Journal of the American Academy of Dermatology marks the latest turn in a dispute over what a large retrospective study can and cannot say about propranolol and infantile hemangioma ulceration. The response, from Kaizhi Zhang, Tong Qiu, Xue Gong, and colleagues at West China Hospital of Sichuan University, answers a Comment by Du et al. that challenged their earlier findings. Both pieces are listed as JAAD Articles in Press, posted ahead of PubMed indexing, which is why neither has surfaced yet in standard literature searches.

The paper under scrutiny is the group's own June 2026 retrospective study of 470 infants with infantile hemangioma treated with oral propranolol, 24 of whom, or 5.1 percent, developed ulceration during treatment. The authors reported that ulceration in this treated group arose at a median age of 3.9 months, compared with 2.0 months in a separate cohort of infants whose ulceration occurred without intervention. They used that gap in timing to argue the treated cases represented a distinct, treatment-associated pattern rather than simple overlap with the hemangioma's natural course, and flagged mixed, indeterminate, and segmental subtypes as risk factors in multivariate analysis.

That argument sits on a fault line that runs through much of the retrospective literature on infantile hemangioma: propranolol is typically started on the more severe or high-risk lesions in the first place, so any comparison between treated and untreated ulceration risks measuring the underlying disease rather than the drug. A single-center design compounds the problem, since how ulceration onset was timed relative to dosing, and how cleanly a comparator group was assembled, both shape whether a age gap of two months reads as signal or as an artifact of case selection.

The stakes of getting the causal direction right are not academic. Propranolol has been the first-line treatment for problematic infantile hemangioma since the FDA approved it as Hemangeol in 2014, and the American Academy of Pediatrics' 2019 guideline recommends titrating to roughly 1 mg/kg per dose through about a year of age. A separate case series, published in 2022, described a paradoxical pattern in which ulceration worsens or newly appears after propranolol is started or its dose raised, a phenomenon researchers have attributed to excessive vasoconstriction, or vascular steal, in tissue that is already compromised. Propranolol is simultaneously the standard treatment for hemangiomas that are already ulcerated, with a prospective JAAD study reporting roughly 93 percent total response by week 24. Whether a given case of post-initiation ulceration reflects the drug causing harm or the drug arriving too late to prevent an ulcer already in motion determines whether clinicians should read it as a warning sign or as expected background noise.

Neither the text of Du et al.'s original Comment nor the substance of the West China Hospital team's rebuttal was accessible for this piece, since ScienceDirect's Articles in Press listing sits outside indexed search and the page could not be retrieved directly. What is available is the chronology: a June 2026 study reporting a statistically later ulceration onset in propranolol-treated infants, a Comment questioning that reading, and a response now posted online as of September 9, with the underlying argument on both sides still locked behind the paywall of a single publisher page.